The rapid advances in biomedical sciences of the past 25 years have resulted in such a level of sophisticated understanding and complicated and labor-intensive technology that investigators must have broad, deep, sophisticated training in molecular science in order to make important contributions. Medical school training no longer provides such training, and M.D. investigators have become progressively less able to compete for research grants and to perform competitive research. We developed an M.D./Ph.D. training program in 1987. The structure of our program is similar to that of other M.D./Ph.D. programs with which we are familiar, including MST's. One especially strong feature of our program is that it is truly a joint undertaking between the medical school and the graduate school. Rather than taking only the basic sciences medical school curriculum, our M.D./Ph.D. students spend about half of their first year in sophisticated graduate school courses that provide them with a broad, deep understanding of the molecular biomedical sciences. We believe that the emergence over the past decade of the University of Alabama at Birmingham as a research-intensive university allows us to offer an excellent program with superb research training opportunities in all of the areas of molecular biomedical science. Our vigorous recruiting efforts have resulted in a steadily increasing number of outstanding applicants from throughout the United States and in a substantial rate of matriculation of applicants we accept. Our current and former students have done very well academically, in their research, in obtaining individual extramural funding, and in obtaining prestigious post-doctoral and faculty positions. The quality o f our program was recognized by our receiving NIH MST funding in 1997. In this proposal we seek continued MST funding for 14 positions and request two additional positions each year for each of the five years of the funding period, for a total of 24 positions. This will provide support for the medical school years.